Influence of Pathophysiological Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease (CAD) impacts the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiological CAD patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularisation and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicentre study enrolled patients with at least one epicardial lesion with an FFR ≤ 0.80 scheduled for PCI. Manual FFR pullbacks were employed to calculate PPG. The primary outcome of optimal revascularisation was defined as a post-PCI FFR ≥ 0.88. RESULTS: 993 patients with 1044 vessels were included. The mean FFR was 0.68 ± 0.12, PPG 0.62 ± 0.17, and post-PCI FFR 0.87 ± 0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65, 95% CI 0.61-0.69, p<0.001) and demonstrated excellent predicted capacity for optimal revascularisation (AUC 0.82, 95% CI 0.79-0.84, p<0.001). Conversely, FFR alone did not predict revascularisation outcomes (AUC 0.54, 95% CI 0.50-0.57). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared to those with focal disease (OR 1.71, 95% CI: 1.00-2.97). CONCLUSIONS: Pathophysiological CAD patterns distinctly affect the safety and effectiveness of PCI. The PPG showed an excellent predictive capacity for optimal revascularisation and demonstrated added value compared to a FFR measurement.

Rationale and design of the pullback pressure gradient (PPG) global registry.

INTRODUCTION: Diffuse disease has been identified as one of the main reasons leading to low post-PCI fractional flow reserve (FFR) and residual angina after PCI. Coronary pressure pullbacks allow for the evaluation of hemodynamic coronary artery disease (CAD) patterns. The pullback pressure gradient (PPG) is a novel metric that quantifies the distribution and magnitude of pressure losses along the coronary artery in a focal-to-diffuse continuum. AIM: The primary objective is to determine the predictive capacity of the PPG for post-PCI FFR. METHODS: This prospective, large-scale, controlled, investigator-initiated, multicenter study is enrolling patients with at least 1 lesion in a major epicardial vessel with a distal FFR ≤ 0.80 intended to be treated by PCI. The study will include 982 subjects. A standardized physiological assessment will be performed pre-PCI, including the online calculation of PPG from FFR pullbacks performed manually. PPG quantifies the CAD pattern by combining several parameters from the FFR pullback curve. Post-PCI physiology will be recorded using a standardized protocol with FFR pullbacks. We hypothesize that PPG will predict optimal PCI results (post-PCI FFR ≥ 0.88) with an area under the ROC curve (AUC) ≥ 0.80. Secondary objectives include patient-reported and clinical outcomes in patients with focal vs. diffuse CAD defined by the PPG. Clinical follow-up will be collected for up to 36 months, and an independent clinical event committee will adjudicate events. RESULTS: Recruitment is ongoing and is expected to be completed in the second half of 2023. CONCLUSION: This international, large-scale, prospective study with pre-specified powered hypotheses will determine the ability of the preprocedural PPG index to predict optimal revascularization assessed by post-PCI FFR. In addition, it will evaluate the impact of PPG on treatment decisions and the predictive performance of PPG for angina relief and clinical outcomes.

Quantitative flow ratio modulated by intracoronary optical coherence tomography for predicting physiological efficacy of percutaneous coronary intervention.

BACKGROUND: The combination of coronary imaging assessment and blood flow perturbation estimation has the potential to improve percutaneous coronary intervention (PCI) guidance. OBJECTIVES: We aimed to evaluate a novel method for fast computation of Murray law-based quantitative flow ratio (µQFR) from coregistered optical coherence tomography (OCT) and angiography (OCT-modulated µQFR, OCT-µQFR) in predicting physiological efficacy of PCI. METHODS: Patients treated by OCT-guided PCI in the OCT-arm of the Fractional Flow Reserve versus Optical Coherence Tomography to Guide RevasculariZAtion of Intermediate Coronary Stenoses trial (FORZA, NCT01824030) were included. Based on angiography and OCT before PCI, simulated residual OCT-µQFR was computed by assuming full stent expansion to the intended-to-treat segment. Plaque composition was automatically characterized using a validated artificial intelligence algorithm. Actual post-PCI OCT-µQFR pullback was computed based on coregistration of angiography and OCT acquired immediately after PCI. Suboptimal functional stenting result was defined as OCT-µQFR ≤ 0.90. RESULTS: Paired simulated residual OCT-µQFR and actual post-PCI OCT-µQFR were obtained in 76 vessels from 74 patients. Simulated residual OCT-µQFR showed good correlation (r = 0.80, p < 0.001), agreement (mean difference = -0.02 ± 0.02, p < 0.001), and diagnostic concordance (79%, 95% confidence interval: 70%-88%) with actual post-PCI OCT-µQFR. Actual post-PCI in-stent OCT-µQFR had a median value of 0.02 and was associated with left anterior descending artery lesion location (ß = 0.38, p < 0.001), higher baseline total plaque burden (ß = 0.25, p = 0.031), and fibrous plaque volume (ß = 0.24, p = 0.026). CONCLUSIONS: This study based on patients enrolled in a prospective OCT-guidance PCI trial shows that simulated residual OCT-µQFR had good correlation, agreement, and diagnostic concordance with actual post-PCI OCT-µQFR. In OCT-guided procedures, OCT-µQFR in-stent pressure drop was low and was significantly predicted by pre-PCI vessel/plaque characteristics.

PCI Deferral Based on Fractional Flow Reserve or Optical Coherence Tomography: Two-Year Results of the Forza Trial.

Backgroud: The "FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty" (FORZA) trial showed that in patients with angiographically intermediate coronary lesions (AICLs), optical coherence tomography (OCT) guidance of percutaneous coronary intervention (PCI) reduced the occurrence of the composite endpoint of major adverse cardiac events (MACE) or significant angina at 13 months, while fractional flow reserve (FFR) guidance was associated with a higher rate of medical management and with lower costs. Safety of PCI deferral when FFR > 0.80 is known, while data on clinical outcomes using an OCT guidance are lacking. We assessed the safety of PCI deferral based on OCT findings. Methods: This is a subgroups analysis of the FORZA Trial focusing on the clinical outcome of patients in whom PCI was originally deferred. In details, patients with AICLs were randomized to FFR or OCT imaging. In the FFR arm, PCI was deferred if FFR was > 0.80 while in the OCT arm in the absence of any of the following conditions: area stenosis > 75%, or 50% to 75% with minimum lumen area < 2.5 mm 2 or plaque rupture. Angina status (evaluated using the Seattle Angina Questionnaire, SAQ), MACE (death, myocardial infarction, target vessel revascularization) and rate of patients treated with optimal medical therapy alone were assessed at 24 months. Results: From a total of 350 patients with 446 AICLs enrolled in the trial (176 randomized to FFR and 174 to OCT), based on the predefined FFR and OCT criteria, PCI was deferred in 119 patients (67.6%) in the FFR arm, and in 82 patients (47.1%) in the OCT arm. At 24-months follow-up, significant residual angina (defined as a value < 90 on the angina frequency scale) was observed in 6 patients (5.0%) in the FFR arm, and in 6 patients (7.3%) in the OCT arm (p = 0.55). Rate of MACE was 10.9% in the FFR arm and 6.1% in the OCT arm (p = 0.32). The number of patients managed by optimal medical therapy alone was still significantly higher using FFR than OCT guidance also at 24 months (60.2% vs 44.2%, p = 0.0038). Conclusions: PCI-deferral based on OCT (using the FORZA trial criteria) is safe and associated with numerically less events at 24-months follow up. FFR guidance is still associated with a higher number of patients managed by optimal medical therapy alone.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

A less-invasive totally-endovascular (LITE) technique for trans-femoral transcatheter aortic valve replacement.

OBJECTIVES: To describe and report the results of an original technique for trans-femoral (TF) transcatheter-aortic-valve-replacement (TAVR). BACKGROUND: TF approach represents the commonest TAVR technique. The best technique for TF-TAVR is not recognized. METHODS: We developed a less-invasive totally-endovascular (LITE) technique for TF-TAVR. The key aspects are: precise TAVR access puncture using angiographic-guidewire-ultrasound guidance radial approach as the "secondary access" (to guide valve positioning, to check femoral-access hemostasis and to manage eventual access-site complications) non-invasive pacing (by retrograde left ventricle stimulation or by definitive pace-maker external programmer) The LITE technique has been systematically adopted at our Institution. Procedure details, complications and clinical events occurring during hospitalization were prospectively recorded. Major vascular complications and life-threatening or major bleedings were the primary study end-points. RESULTS: A total of 153 consecutive patients referred for TF-TAVR were approached using the LITE technique. Mean predicted surgical operative mortality was 4.9% and mean TAVR predicted mortality was 3.9%. In 132 (86.3%) patients, TAVR was completed without the need for additional femoral artery access or transvenous temporary pace-maker implantation. Major vascular complications occurred in 2 (1.3%), life-threatening or major bleedings occurred in 4 (2.6%) patients. All-cause death occurred in 3 patients (2.0%). CONCLUSIONS: TF-TAVR according to LITE technique is feasible and is associated with very low rates of vascular or bleeding complications.

Predictive factors of discordance between the instantaneous wave-free ratio and fractional flow reserve.

OBJECTIVES: To identify clinical, angiographic and hemodynamic predictors of discordance between instantaneous wave-free ratio (iFR) and fractional flow reserve (FFR). BACKGROUND: The iFR was found to be non-inferior to the gold-standard FFR for guiding coronary revascularization, although it is discordant with FFR in 20% of cases. A better understanding of the causes of discordance may enhance application of these indices. METHODS: Both FFR and iFR were measured in the prospective multicenter CONTRAST study. Clinical, angiographic and hemodynamic variables were compared between patients with concordant values of FFR and iFR (cutoff ≤0.80 and ≤0.89, respectively). RESULTS: Out of the 587 patients included, in 466 patients (79.4%) FFR and iFR agreed: both negative, n = 244 (41.6%), or positive, n = 222 (37.8%). Compared with FFR, iFR was negative discordant (FFR+/iFR-) in 69 (11.8%) patients and positive discordant (FFR-/iFR+) in 52 (8.9%) patients. On multivariate regression, stenosis location (left main or proximal left anterior descending) (OR: 3.30[1.68;6.47]), more severe stenosis (OR: 1.77[1.35;2.30]), younger age (OR: 0.93[0.90;0.97]), and slower heart rate (OR: 0.59[0.42;0.75]) were predictors of a negative discordant iFR. Absence of a beta-blocker (OR: 0.41[0.22;0.78]), older age (OR: 1.04[1.00;1.07]), and less severe stenosis (OR: 0.69[0.53;0.89]) were predictors of a positive discordant iFR. CONCLUSIONS: During iFR acquisition, stenosis location, stenosis degree, heart rate, age and use of beta blockers influence concordance with FFR and should be taken into account when interpreting iFR.

Long-Term Outcomes of Extent of Revascularization in Complex High Risk and Indicated Patients Undergoing Impella-Protected Percutaneous Coronary Intervention: Report from the Roma-Verona Registry.

OBJECTIVE: To investigate the effect of extent of revascularization in complex high-risk indicated patients (CHIP) undergoing Impella-protected percutaneous coronary intervention (PCI). BACKGROUND: Complete revascularization has been shown to be associated with improved outcomes. However, the impact of more complete revascularization during Impella-protected PCI in CHIP has not been reported. METHODS: A total of 86 CHIP undergoing elective PCI with Impella 2.5 or Impella CP between April 2007 and December 2016 from 2 high volume Italian centers were included. Baseline, procedural, and clinical outcomes data were collected retrospectively. Completeness of coronary revascularization was assessed using the British Cardiovascular Intervention Society myocardial jeopardy score (BCIS-JS) derived revascularization index (RI). The primary end-point was all-cause mortality. A multivariate regression model was used to identify independent predictors of mortality. RESULTS: All patients had multivessel disease and were considered unsuitable for surgery. At baseline, 44% had left main disease, 78% had LVEF ≤ 35%, and mean BCIS-JS score was 10±2. The mean BCIS-JS derived RI was 0.7±0.2 and procedural complications were uncommon. At 14-month follow-up, all-cause mortality was 10.5%. At follow-up, 67.4% of CHIP had LVEF ≥ 35% compared to 22.1% before Impella protected-PCI. Higher BCIS-JS RI was significantly associated with LVEF improvement (p=0.002). BCIS-JS RI of ≤ 0.8 (HR 0.11, 95% CI 0.01- 0.92, and p = 0.042) was an independent predictor of mortality. CONCLUSIONS: These results support the practice of percutaneous Impella use for protected PCI in CHIP. A more complete revascularization was associated with significant LVEF improvement and survival.

Percutaneous transcatheter aortic valve replacement induces femoral artery shrinkage: angiographic evidence and predictors for a new side effect.

OBJECTIVES: We sought to investigate the possible impact of transaortic valve replacement (TAVR) on common femoral artery (CFA) integrity as assessed by angiography. BACKGROUND: CFA represents the most adopted access for TAVR but various degrees of vascular damage may be induced by the procedure. METHODS: Patients underwent percutaneous transfemoral TAVR who had both pre- and post-TAVR access-site angiography were retrospectively selected. Clinical and procedural data (including technique and complications) were prospectively recorded into a structured TAVR database. Pre-TAVR and post-TAVR angiograms were analyzed using a quantitative angiographic analysis software to assess reference diameters, minimum luminal diameter (MLD), and percentage of diameter stenosis (DS). RESULTS: A total of 124 patients entered the study (mean age: 85 years, mean Euroscore II: 10%). ProStar (13.5%) and double ProGlide (82.2%) preclosure were the main hemostatic techniques. CFA exhibited a significant shrinkage with TAVR as assessed by significant MLD reduction (5.6 mm after TAVR vs. 6.8 mm before, P < .001) and DS increase (30.3% after vs. 17.0%, P < .001). Such differences remained statistically significant after exclusion of 18 patients (14.2%) who had (minor or major) vascular complications. At multivariable analysis, pre-TAVR DS (P = .03) and history of peripheral arterial disease (P = .01), were significantly associated with vascular complications. CONCLUSIONS: Percutaneous TAVR induces an angiographically detectable CFA lumen reduction. Such findings call for further studies assessing clinical impact of this phenomenon and open the door for further refinements of the TAVR access management aimed at preserving vessel integrity.

Granulocyte colony-stimulating factor for the treatment of cardiovascular diseases: An update with a critical appraisal.

Heart failure and acute myocardial infarction are conditions that are associated with high morbidity and mortality. Significant dysfunction of the heart muscle can occur as the consequence of end-stage chronic cardiovascular diseases or acute ischemic events that are marked by large infarction area and significant tissue necrosis. Despite the remarkable improvement of conventional treatments, a substantial proportion of patients still develops severe heart failure that can only be resolved by heart transplantation or mechanical device implantation. Therefore, novel approaches based on stem-cell therapy can directly modify the disease process and alter its prognosis. The ability of the stem-cells to modify and repair the injured myocardium is a challenging but intriguing concept that can potentially replace expensive and invasive methods of treatment that are associated with increased risks and significant financial costs. In that sense, granulocyte colony-stimulating factor (G-CSF) seems as an attractive treatment approach. Based on the series of pre-clinical experiments and a limited amount of clinical data, it was demonstrated that G-CSF agents possess the ability to mobilize stem-cells from bone marrow and induce their differentiation into cardiomyocytes or endothelial cells when brought into contact with injured regions of the myocardium. However, clinical benefits of G-CSF use in damaged myocardium remain unclear and are the topic of expert discussion. The main goal of this review is to present relevant and up-to-date evidence on G-CSF therapy use in pre-clinical models and in humans and to provide a rationale for its potential clinical applications in the future.

Impact of drug-eluting balloon (pre- or post-) dilation on neointima formation in de novo lesions treated by bare-metal stent: the IN-PACT CORO trial.

UNLABELLED: The efficacy of DEB in modifying the high restenosis risk associated with BMS implantation is doubtful. Optical coherence tomography (OCT) may allow precise assessment of neointimal formation after stent implantation. We performed a single-center, prospective, 1:2 randomized trial comparing BMS implantation alone (BMS group) vs. additional DEB (DEB group). DEB patients were further randomized 1:1 to DEB before stenting (pre-DEB group), or after stenting (post-DEB group). Primary endpoint was OCT-assessed neointimal hyperplasia (expressed both as mean in-stent neointimal area and as percentage obstruction of the mean stent area) at 6 months. Secondary endpoints were the percentage of uncovered and malapposed stent struts. Thirty patients were enrolled and randomized to BMS (n = 10), pre-DEB (n = 10), post-DEB (n = 10). At 6-month OCT follow-up, DEB significantly reduced neointimal area compared with BMS: mean neointimal area 2.01 ± 0.89 vs. 3.03 ± 1.07 mm(2) (p = 0.02), percentage area obstruction 24.56 ± 12.50 vs. 37.51 ± 12.26 % (p = 0.02). The percentage of uncovered and malapposed stent struts did not differ significantly between BMS and DEB. In the comparison between pre-DEB and post-DEB, no significant difference was observed for both primary and secondary endpoints. In de novo coronary lesions treated with BMS, DEB use could be associated with a mild reduction in neointimal hyperplasia at 6 months; this effect could be unrelated to the timing of DEB dilation (pre- or post-stenting). CLINICAL TRIAL REGISTRATION INFORMATION: http://www.clinicaltrials.gov . Identifier: NCT01057563.

In vitro cardiomyocyte differentiation of umbilical cord blood cells: crucial role for c-kit(+) cells.

BACKGROUND AIMS: Although bone marrow c-kit(+) progenitor cells support myocardial regeneration, the cardiomyocyte differentiation potential of umbilical cord blood (UCB) c-kit(+) cells is unknown. METHODS: UCB mononuclear cells (MNCs) and c-kit(+) cells purified by use of immunomagnetic beads were used. Cardiomyocyte differentiation was induced with (i) α-minimum essential medium (MEM) with cyclosporine A, (ii) α-MEM with bone morphogenic protein 4 (BMP-4) and transforming growth factor-ß (TGF-ß) or (iii) MEM with dexamethasone. The expression of cardiac markers (GATA4, GATA6, ß-myosin heavy chain, α-sarcomeric actin and cardiac Troponin T) was investigated, and whole-cell current and voltage-clamp recordings were performed. RESULTS: Although c-kit(+) cells revealed an immature gene profile, with high expression of CD34, CD133, aldehyde dehydrogenase-A1 and c-myc RNAs, purified c-kit(+) cells did not succeed in differentiating into cardiomyocyte-like cells in culture. In contrast, MNCs (either in α-MEM plus cyclosporine A or in α-MEM plus BMP-4 and TGF-ß) produced large, adherent cells expressing several cardiac genes and exhibiting an excitable phenotype. Cardiomyocyte-like cell formation was prevented by removing the c-kit(+) cell fraction from MNCs. Furthermore, after co-culturing carboxyfluorescein diacetate succynimidyl ester (CFSE)-tracked c-kit(+) cells together with c-kit(-) cells, we found that cardiac Troponin T--expressing cells were also CFSE(+). CONCLUSIONS: We show that UCB contains progenitors endowed with differentiation potential into cardiomyocytes: these cells reside in the c-kit(+) fraction and require the presence of abundant accessory cells to accomplish the differentiation. These preliminary observations provide the basis for consider the storage of autologous UCB in patients with prenatal diagnosis of congenital heart diseases potentially amenable by myocardial regenerative approaches.

Clinical and procedural impact of aortic arch anatomic variants in carotid stenting procedures.

OBJECTIVES: To evaluate the impact of aortic arch variants in patients undergoing carotid artery stenting (CAS). BACKGROUND: CAS is increasingly carried out to treat the patients with internal carotid artery (ICA) stenosis. Aortic arch anatomy may influence its feasibility and affect clinical outcome. METHODS: Aortic arch digital subtraction angiography was systematically performed before CAS. Aortic arch elongation and bovine arch variants were recorded. Catheter manipulation time (CMT) was assessed for each patient. Adverse cardiovascular and cerebral events were assessed at 30 days. RESULTS: A total of 282 consecutive patients undergoing CAS under proximal balloon occlusion (57.8%) or distal filter (42.2%) neuroprotection were enrolled (age, 72 ± 7 years; 72.7% males). Type II and III elongation variants were detected in 23.4% and 10.6% of patients, respectively; in total, 20.5% of the patients had bovine configuration. CMT was significantly influenced by aortic elongation (56.1 ± 16.5 min in patients with type III aortic arch configuration compared to 38.2 ± 11.6 min in patients with type I or type II, P < 0.01) and (in left ICA) by bovine configuration (49.2 ± 11.4 min in bovine variants vs. 37.7 ± 11.5 min in patients with nonbovine anatomy, P < 0.001). CMT, but not aortic arch anatomy, resulted the only independent predictor of 30-day adverse outcome (hazard ratio [HR], 1.07; 95% confidence interval [CI], 1.03-1.10, P < 0.01). CONCLUSIONS: Adverse aortic arch anatomies are frequently encountered in CAS procedures and are associated to longer procedural times. A longer CMT increases the risk for adverse outcome. These data suggest that a careful procedure planning aimed at a reduction of CMT may be pivotal to improve the safety of CAS procedures.

Endothelial progenitor cells in morbid obesity.

BACKGROUND: The aim of this study was to assess the relationship among anthropometric indexes of adiposity (body mass index [BMI], waist circumference [WC]), endothelial progenitor cells (EPC) and carotid intima-media thickness (IMT) in patients with morbid obesity, and the effect of diabetes and weight loss. METHODS AND RESULTS: BMI, WC, IMT and circulating EPC (defined as CD34+/KDR+/CD45- cells) were assessed in 100 patients (37 with diabetes). Fifty patients underwent bariatric surgery, and in 48 of them a complete re-assessment after an average follow-up of 252±108 days was carried out. In 29 of them subcutaneous and visceral adipose tissue samples were obtained at the time of intervention and analyzed for the presence and number of EPC. EPC were directly correlated with weight, BMI, WC and insulin level, and inversely with mean IMT. All correlations were confined to non-diabetic patients. EPC were found in both subcutaneous and visceral adipose tissue specimens. Circulating EPC significantly decreased after weight loss (P=0.002). CONCLUSIONS: EPC are positively related to markers of adiposity in severe obesity, when not complicated by diabetes. Weight loss is associated with decrease in EPC level. EPC are inversely correlated with IMT, confirming their protective role also in severe obesity. Diabetes has a negative modulating action.

[An exemplificative case of constrictive pericarditis]. / Un caso esemplare, ma soprattutto esemplificativo, di pericardite costrittiva.

Constrictive pericarditis is a rare, but fatal disease, leading to heart failure due to diastolic dysfunction resulting from the fibrotic and non-elastic pericardium. Clinical presentation is sneaky, with initial symptoms of splanchnic and peripheral venous congestion, then with hepatomegaly and ascites: this kind of presentation is not often recognized, delaying diagnosis. We report the case of a young male adult with no previous cardiovascular history, but with a diagnosis of hepatic cirrhosis: investigations in our Centre led to the diagnosis of constrictive pericarditis, successfully treated with pericardiectomy; however, despite the effective venous decongestion, it was not possible to spare the patient from liver transplant.

Ischemia with non-obstructive coronary artery (INOCA): Non-invasive versus invasive techniques for diagnosis and the role of #FullPhysiology.

Ischemia with non-obstructive coronary arteries (INOCA) is an increasingly recognized entity. It encompasses different pathophysiological subtypes (i.e., endotypes), including coronary microvascular dysfunction (CMD), vasospastic angina (VSA) and mixed entities resulting from the variable combination of both. Diagnosing INOCA and precisely characterizing the endotype allows for accurate medical treatment and has proven prognostic implications. A breadth of diagnostic technique is available, ranging from non-invasive approaches to invasive coronary angiography adjuvated by functional assessment and provocative tests. This review summarizes the strength and limitations of these methodologies and provides the rationale for the routine referral for invasive angiography and functional assessment in this subset of patients.

"The INOCA-IT: Rationale and design of a multicenter registry investigating ischemia in patients with non-obstructive coronary artery (INOCA) disease in Italy".

BACKGROUND: Ischemia with non-obstructive coronary artery (INOCA) disease is being progressively acknowledged as one of the pathophysiological mechanisms of chronic coronary syndrome (CCS) in an increasingly wide range of clinical pictures. Although the research has already begun to move towards a defined diagnostic pathway and a specific medical therapy for this disease, at present it remains a clinical challenge, especially if not thoroughly investigated. METHODS AND RESULTS: The INOCA IT Multicenter Registry RF-2019-12369486 is a prospective, multicentric, non-randomized, single-arm, open label clinical study which aims to evaluate the efficacy of a stratified diagnostic and therapeutic approach on adverse events prevention and symptom relief in Italian patients with INOCA disease. The study population includes patients with a clinical presentation of CCS for angina and/or positive stress test for myocardial ischemia and evidence of non-obstructive coronary artery disease (CAD) at coronary angiography. In these patients a complete invasive coronary physiology assessment is performed with the guidewire-based measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), followed by acetylcholine (ACh) spasm provocation test. On the basis of the results of coronary function testing, patients are stratified into different INOCA endotypes (coronary microvascular disease, vasospastic angina, microvascular spasm, non-cardiac chest pain) and given a tailored medical therapy in accordance with the latest scientific evidence. At one year follow-up the impact of such a target therapy on angina class and quality of life, as well as on cardiovascular adverse events (hospitalization and coronary revascularization) is evaluated. CONCLUSIONS: The INOCA-IT Multicenter Registry will inform clinicians on sex-specific prevalence of INOCA in Italy and will show the impact of a stratified diagnostic and therapeutic approach on symptoms burden and prognosis of INOCA patients.

Coronary Physiology Guidance vs Conventional Angiography for Optimization of Percutaneous Coronary Intervention: The AQVA-II Trial.

BACKGROUND: The debate surrounding the efficacy of coronary physiological guidance compared with conventional angiography in achieving optimal post-percutaneous coronary intervention (PCI) fractional flow reserve (FFR) values persists. OBJECTIVES: The primary aim of this study was to demonstrate the superiority of physiology-guided PCI, using either angiography or microcatheter-derived FFR, over conventional angiography-based PCI in complex high-risk indicated procedures (CHIPs). The secondary aim was to establish the noninferiority of angiography-derived FFR guidance compared with microcatheter-derived FFR guidance. METHODS: Patients with obstructive coronary lesions and meeting CHIP criteria were randomized 2:1 to receive undergo physiology- or angiography-based PCI. Those assigned to the former were randomly allocated to angiography- or microcatheter-derived FFR guidance. CHIP criteria were long lesion (>28 mm), tandem lesions, severe calcifications, severe tortuosity, true bifurcation, in-stent restenosis, and left main stem disease. The primary outcome was invasive post-PCI FFR value. The optimal post-PCI FFR value was defined as >0.86. RESULTS: A total of 305 patients (331 study vessels) were enrolled in the study (101 undergoing conventional angiography-based PCI and 204 physiology-based PCI). Optimal post-PCI FFR values were more frequent in the physiology-based PCI group compared with the conventional angiography-based PCI group (77% vs 54%; absolute difference 23%, relative difference 30%; P < 0.0001). The occurrence of the primary outcome did not differ between the 2 physiology-based PCI subgroups, demonstrating the noninferiority of angiography- vs microcatheter-derived FFR (P < 0.01). CONCLUSIONS: In CHIP patients, procedural planning and guidance on the basis of physiology (through either angiography- or microcatheter-derived FFR) are superior to conventional angiography for achieving optimal post-PCI FFR values. (Physiology Optimized Versus Angio-Guided PCI [AQVA-II]; NCT05658952).